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- Alvarado-kristensson, Maria
(författare)
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γ-tubulin as a signal-transducing molecule and meshwork with therapeutic potential
- 2018
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Ingår i: Signal Transduction and Targeted Therapy. - : Springer Science and Business Media LLC. - 2059-3635. ; 3
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Forskningsöversikt (refereegranskat)abstract
- Knowledge of γ-tubulin is increasing with regard to the cellular functions of this protein beyond its participation in microtubule nucleation. γ-Tubulin expression is altered in various malignancies, and changes in the TUBG1 gene have been found in patients suffering from brain malformations. This review recapitulates the known functions of γ-tubulin in cellular homeostasis and discusses the possible influence of the protein on disease development and cancer.
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| 4. |
- Chen, Y, et al.
(författare)
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miR-124/VAMP3 is a novel therapeutic target for mitigation of surgical trauma-induced microglial activation
- 2019
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Ingår i: Signal transduction and targeted therapy. - : Springer Science and Business Media LLC. - 2059-3635. ; 4, s. 27-
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Tidskriftsartikel (refereegranskat)abstract
- Activation of microglia and the subsequently elevated inflammatory cytokine release in the brain during surgery predispose individuals to cognitive dysfunction, also known as postoperative cognitive dysfunction (POCD). miR-124 is one of the most abundant microRNAs in the brain that regulates microglial function. Elucidating the role of miR-124 in microglial activation in the context of surgery may therefore promote understanding of as well as therapeutic development for post-surgical disorders involving microglial activation. The downstream targets of miR-124 were investigated using bioinformatic screening and dual-luciferase reporter assay validation, and vesicle-associated membrane protein 3 (VAMP3) was identified as a potential target. The kinetics of miR-124/VAMP3 expression was first examined in vitro in microglial cells (primary microglia and BV2 microglial cells) following lipopolysaccharide (LPS) stimulation. LPS induced a time-dependent decrease of miR-124 and upregulated the expression of VAMP3. Manipulating miR-124/VAMP3 expression by using miR-124 mimics or VAMP3-specific siRNA in LPS-stimulated BV2 microglial cells inhibited BV2 microglial activation-associated inflammatory cytokine release. To further examine the role of miR-124/VAMP3 in a surgical setting, we employed a rat surgical trauma model. Significant microglial activation and altered miR-124/VAMP3 expression were observed following surgical trauma. We also altered miR-124/VAMP3 expression in the rat surgical trauma model by administration of exogenous miR-124 and by using electroacupuncture, which is a clinically applicable treatment that modulates microglial function and minimizes postoperative disorders. We determined that electroacupuncture treatment specifically increases the expression of miR-124 in the hypothalamus and hippocampus. Increased miR-124 expression with a concomitant decrease in VAMP3 expression resulted in decreased inflammatory cytokine release related to microglial activation post-surgery. Our study indicates that miR-124/VAMP3 is involved in surgery-induced microglial activation and that targeting miR-124/VAMP3 could be a potential therapeutic strategy for postoperative disorders involving microglial activation.
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| 9. |
- Jing, YK, et al.
(författare)
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SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism
- 2021
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Ingår i: Signal transduction and targeted therapy. - : Springer Science and Business Media LLC. - 2059-3635. ; 6:1, s. 345-
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Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 infection causes severe immune disruption. However, it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients. In our study, we have characterized the immune phenotype of B cells from 15 recovered COVID-19 patients, and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation, but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation. However, the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation. Interestingly, we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients. Moreover, the BCR signaling and early B-cell response were disrupted upon BCR stimulation. Mechanistically, we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism. In conclusion, we found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism, which may provide a new intervention target to cure COVID-19.
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